{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:44:33Z","timestamp":1779090273503,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mosaic disorders affecting pigmentation are a large group of different, rare diseases that present with hypo- and\/or hyperpigmented birthmarks. These can carry associated risks such as involvement of other organ systems, a predisposition to cancer and the possibility of transmission to future offspring as germline disease. This review draws on the clinical and genetic discoveries of the last decade to discuss how to make a genetic diagnosis in mosaic disorders affecting pigmentation. Practicalities reviewed include how to take the right samples for testing and how to process the samples correctly, while key concepts include understanding variant allele frequency, variants of uncertain significance and sensitivity of genetic testing. It then goes on to demonstrate how to use the clinical classification established in part 1 of this two-part review to decide which genetic tests to perform and in which order. All currently known genetic causes of mosaic disorders affecting pigmentation are detailed, along with which genes have variants with the potential for germline transmission to the next generation.<\/jats:p>","DOI":"10.1093\/bjd\/ljaf224","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T11:51:10Z","timestamp":1753271470000},"page":"1047-1055","source":"Crossref","is-referenced-by-count":3,"title":["Mosaic disorders affecting pigmentation \u2013 part 2: how to make a genetic diagnosis"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6256-327X","authenticated-orcid":false,"given":"Veronica A","family":"Kinsler","sequence":"first","affiliation":[{"name":"NHS England Rare Disease Collaborative Network for Mosaic Disorders, Paediatric Dermatology Department, Great Ormond Street Hospital for Children , London ,","place":["UK"]},{"name":"Genetics and Genomic Medicine programme, UCL Great Ormond Street Institute of Child Health , London ,","place":["UK"]},{"name":"Mosaicism and Precision Medicine Laboratory, the Francis Crick Institute , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"2025111813172795200_ljaf224-B1","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1038\/bjc.2017.49","article-title":"MEK inhibition appears to improve symptom control in primary NRAS-driven CNS melanoma in children","volume":"116","author":"Kinsler","year":"2017","journal-title":"Br J Cancer"},{"key":"2025111813172795200_ljaf224-B2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.jid.2023.06.213","article-title":"Mosaic BRAF fusions are a recurrent cause of congenital melanocytic nevi targetable by MAPK pathway inhibition","volume":"144","author":"Martin","year":"2024","journal-title":"J Invest Dermatol"},{"key":"2025111813172795200_ljaf224-B3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/2051-5960-2-41","article-title":"Experimental treatment of NRAS-mutated neurocutaneous melanocytosis with MEK162, a MEK-inhibitor","volume":"2","author":"Kusters-Vandevelde","year":"2014","journal-title":"Acta Neuropathol Commun"},{"key":"2025111813172795200_ljaf224-B4","doi-asserted-by":"crossref","first-page":"e20182469","DOI":"10.1542\/peds.2018-2469","article-title":"Giant congenital melanocytic nevus treated with trametinib","volume":"143","author":"Mir","year":"2019","journal-title":"Pediatrics"},{"key":"2025111813172795200_ljaf224-B5","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1111\/bjd.21851","article-title":"Giant congenital melanocytic naevus with a novel CUX1\u2013BRAF fusion mutation treated with trametinib","volume":"187","author":"Molho-Pessach","year":"2022","journal-title":"Br J Dermatol"},{"key":"2025111813172795200_ljaf224-B7","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jid.2024.04.031","article-title":"RNA therapy for oncogenic NRAS-driven nevi induces apoptosis","volume":"145","author":"Bryant","year":"2025","journal-title":"J Invest Dermatol"},{"key":"2025111813172795200_ljaf224-B6","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/bjd.17924","article-title":"Mosaic abnormalities of the skin: review and guidelines from the European Reference Network for rare skin diseases","volume":"182","author":"Kinsler","year":"2020","journal-title":"Br J Dermatol"},{"key":"2025111813172795200_ljaf224-B8","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1038\/jid.2013.70","article-title":"Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS","volume":"133","author":"Kinsler","year":"2013","journal-title":"J Invest Dermatol"},{"key":"2025111813172795200_ljaf224-B9","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/bjd.18106","article-title":"Does the gene matter? 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